DUF1220 Domain
DUF1220 is a protein domain of unknown function that shows a striking human lineage-specific (HLS) increase in copy number and is associated with human brain evolution. DUF1220 domains are approximately 65 amino acids in length and are encoded by a two-exon doublet. In the human genome, DUF1220 sequences are located primarily on chromosome 1 in region 1q21.1-q21.2, with several copies also found at 1p36, 1p13.3, and 1p12. Sequences encoding DUF1220 domains show signs of positive selection, especially in primates, and are expressed in several human tissues including brain, where their expression is restricted to neurons.
The copy number of the DUF1220 domain increases as a function of a species evolutionary proximity to humans. DUF1220 copy number is highest in humans, having over 270 copies, with person-to-person variations in copy number, and shows the largest HLS increase in copy number (an additional 160 copies) of any protein coding region in the human genome. DUF1220 copy number is reduced in African great apes (estimated 125 copies in chimpanzees), further reduced in orangutan (92) and Old World monkeys (35), single- or low-copy in non-primate mammals and absent in non-mammals.
Autism Spectrum Disorders (ASDs)
ASDs are a group of developmental disabilities that can cause significant social, communication and behavioral challenges. ASDs are “spectrum disorders” that affect each person in different ways, and can range from very mild to severe. People with ASDs share some similar symptoms, such as problems with social interaction. But there are differences in when the symptoms start, how severe they are, and the exact nature of the symptoms.
There are three different types of ASDs:                1) Autistic Disorder (also called “classic” autism)        
People with autistic disorder usually have significant language delays, social and communication challenges, and unusual behaviors and interests. Many people with autistic disorder also have intellectual disability.
2) Asperger Syndrome
People with Asperger syndrome usually have some milder symptoms of autistic disorder. They might have social challenges and unusual behaviors and interests. However, they typically do not have problems with language or intellectual disability.
3) Pervasive Developmental Disorder—Not Otherwise Specified (PDD-NOS; also called “atypical autism”)
People who meet some of the criteria for autistic disorder or Asperger syndrome, but not all, may be diagnosed with PDD-NOS. People with PDD-NOS usually have fewer and milder symptoms than those with autistic disorder. The symptoms might cause only social and communication challenges.
ASDs begin before the age of 3 and last throughout a person's life, although symptoms may improve over time. Some children with ASD show hints of future problems within the first few months of life. In others, symptoms might not show up until 24 months or later. Some children with ASD seem to develop normally until around 18 to 24 months of age and then they stop gaining new skills, or they lose the skills they once had.
Head circumference has also been implicated in degree of impairment in affected individuals, such that increased head circumference is associated with increasing symptom severity (Davis J M, Keeney J G, Sikela J M, Hepburn S (2013) Mode of Genetic Inheritance Modifies the Association of Head Circumference and Autism-Related Symptoms: A Cross-Sectional Study. PLoS ONE 8:e74940. doi: 10.1371/journal.pone.0074940). However, the opposite association has also been found (Dementieva Y A, Vance D D, Donnelly S L, et al (2005) Accelerated head growth in early development of individuals with autism. Pediatr Neurol 32:102-108. doi: 10.1016/j.pediatrneuro1.2004.08.005), which suggests a complex etiologic relationship with brain growth. Considering the vast clinical heterogeneity of autism presentation and that much of the phenotype is based on clinical review and parent report, it may also be expected that association studies of biological indicators, such as head circumference or various genetic markers, may not replicate across populations in different studies.
Thus, diagnosing ASDs can be difficult because there is currently no approved medical test to diagnose the disorders. Doctors look at the child's behavior and development to make a diagnosis. ASDs can sometimes be detected at 18 months or younger. By age 2, a diagnosis by an experienced professional can be considered very reliable. However, many children do not receive a final diagnosis until much older. This delay means that many children with ASD do not get the help they need.
Thus, there remains a need for a reliable medical test to predict the severity of the social impairment in an individual diagnosed with autism.